On the Governing Mechanisms of Chiral Resolution by Viedma Ripening

Abstract

The chirality of molecules is an important phenomenon in chemistry and biology, which has far-reaching consequences in the fine chemicals and pharmaceuticals industry. The two mirrored forms, or enantiomers, of a chiral molecule can have different physiological effects, and thus the separation of the two enantiomers is an important unit operation in industry. Viedma ripening is a novel crystallisation process which can accomplish such a chiral resolution without the use of any chiral auxiliaries and without detailed kinetic and thermodynamics characterisation of the system. In this process, a suspension of conglomerate crystals is mechanically or thermally processed in the presence of a racemisation reaction in solution, and with time, the solid phase is converted to single chirality. The mechanisms proposed to explain Viedma ripening are crystal breakage, agglomeration, growth and dissolution due to the sizedependence of solubility, and solution phase racemisation. In order to show that this set of mechanisms is plausible and to improve our understanding of the process, a population balance model incorporating all of these models was developed. This is possible since the framework of population balance models is an established technique for the mathematical description of crystallisation processes, and each of the mechanisms mentioned above has described within this framework previously.